DNA hypomethylation mediated transcription dysregulation participates in pathogenesis of polycystic ovary syndrome

Am J Pathol. 2024 Feb 23:S0002-9440(24)00072-5. doi: 10.1016/j.ajpath.2024.02.003. Online ahead of print.ABSTRACTPolycystic ovary syndrome is a highly heterogenous and genetically complex endocrine disorder. Although the etiology remains mostly elusive, growing evidences suggested abnormal changes of DNA methylation correlate well with systemic and tissue-specific dysfunctions in polycystic ovary syndrome. Dehydroepiandrosterone-induced polycystic ovary syndrome-like mouse model was generated, which has similar metabolic and reproductive phenotype as human polycystic ovary syndrome patients, and used to experimentally validate potential role of aberrant DNA methylation in polycystic ovary syndrome in this study. Integrated DNA methylation and transcriptome analysis revealed potential role of genomic DNA hypomethylation in transcription regulation of polycystic ovary syndrome and identified several key candidate genes, including BMP4, Adcy7, Tnfaip3, and Fas, which were regulated by aberrant DNA hypomethylation. Moreover, intraperitoneal injection of S-adenosylmethionine increased overall DNA methylation level of polycystic ovary syndrome-like mice and restored expression of the candidate genes to similar levels as the control, alleviating reproductive and metabolic abnormalities in polycystic ovary syndrome-like mice. These findings provided direct evidence showing the importance of normal DNA methylation in epigenetic regulation of polycystic ovary syndrome and potential tar...
Source: Am J Pathol - Category: Pathology Authors: Source Type: research